Study shows how physical activity helps prevent metabolic diseases

In an experiment conducted by EACH-USP, regular exercise prevented mice that were fed chocolate, peanuts, cookies and sugar from developing insulin resistance.

By Karina Toledo

Agência FAPESP – A study conducted by Universidade de São Paulo’s Arts, Sciences and Humanities School (EACH-USP) has uncovered some of the metabolic mechanisms through which physical activity helps to prevent health problems, such as diabetes and the accumulation of fat in the liver, caused by poor eating habits.

The experiment was conducted with mice that received feed with added chocolate, Marie biscuits, peanuts and sugar. The diet, given the name Cafeteria, had the objective of mimicking the eating habits of humans, explains Fabiana de Sant'Anna Evangelista, coordinator of the study funded by FAPESP under its Regular Research grant program.

“We standardized this diet in a previous study and saw that after six weeks of eating this mixture, the animals had developed glucose intolerance, insulin resistance and obesity,” explains Evangelista .

Although the caloric value of the Cafeteria diet is not very different from that of normal feed (4.23 kilocalories per gram (kcal/g) compared to 3.78 kcal/g, respectively),  the fat level of the Cafeteria diet (18.74%) is much higher than that of normal feed (4%).  The protein level, by contrast, decreases from 22% in standard feed to 15% in the Cafeteria diet. The fiber content is also reduced, from 6% in standard feed to 3.24% in the Cafeteria diet . Although the percentage of carbohydrates in the two diets is similar at approximately 55%, the carbohydrates in the Cafeteria diet have a higher glycemic index.

“Because this diet tastes good, it sets off a compulsive behavior. The animals start eating for pleasure, like humans. This leads to higher caloric ingestion, an increase in adiposity and glycemia , and greater resistance to insulin action,” comment the researchers .

To verify whether regular physical activity was capable of preventing these problems, the animals were submitted to a two-month training program, which included 1  hour of physical aerobic exercise on a treadmill at moderate intensity five days per week.

The mice were split into three groups. The first, which was considered the control group, received normal feed and remained sedentary. The second group received the Cafeteria feed and did not perform physical activity. The third group received the Cafeteria diet and was included in the physical training program.

Whereas weight increased 13.3% in the sedentary control group, the sedentary animals receiving the Cafeteria feed showed a weight increase of 21.3%. The animals that performed physical activity  saw their weight increase by 8.7%, and they did not develop hyperglycemia, glucose intolerance or insulin resistance. Furthermore, they had much more much smaller increases in cholesterol increases in cholesterol.

“It was interesting to see what happened in the adipose tissues of the two groups that received the Cafeteria diet. It was evident that physical exercise prevented the hypertrophy of adipose cells and, consequently, the alteration of cell signaling that contributes to regular energetic metabolism,” affirms Evangelista.

Crossed signals

In sedentary animals, the hypertrophied adipose cells began to secrete more pro-inflammatory substances and less adiponectin – an essential protein for maintaining the proper functioning of the mechanisms responsible for capturing glucose.

"This set of alterations leads to insulin resistance, and it is only a matter of time for this condition to develop into type 2 diabetes," explains Evangelista.

Hypertrophied adipocytes also begin to produce more leptin, the hormone responsible for activating two important responses in the organism: the inhibition of appetite and the stimulation of energetic metabolism.

“But when the adipose mass and the production of leptin increase significantly, the organism becomes resistant to the action of this hormone [leptin] because of the loss of sensitivity of the receptors, and all signaling of satiety and resting energetic expenditure is compromised,” she explains.

Because the amount of adipose tissue did not increase in animals that exercised, the leptin level remained stable  and continued to play its role in controlling appetite and stimulating energetic metabolism.

An analysis of adipose tissue also revealed that animals that engage in physical activity have higher concentrations of citrate synthase, an essential enzyme in the oxidation of fat molecules to provide energy. “Production of this enzyme is stimulated by mitochondrial activity, which increases with exercise,” comments Evangelista.

Additionally, training not only increases energy consumption in skeletal muscle tissues but also, as expected, increases the energetic metabolism of adipose tissue.
 
Balanced energy

According to Evangelista, sedentary animals fed the Cafeteria diet began to produce less of a protein called AMPK, which is fundamental to the balance between lipolytic activity (breaking down fat for consumption) and lipogenic activity (storage of fat in adipose tissue).

The researchers found that the Cafeteria diet induced an increase in lipolytic activity in the two groups of mice. In other words, more molecules of fat were being broken down and entering the circulatory system to be transformed into energy.

But because the sedentary mice did not have a mechanism for oxidizing these fatty acids and using them  as a source of energy, lipids ended up entering the liver, where they accumulate and cause ‘fatty liver’, or hepatic steatosis. Some of the fat returns to adipose tissues and is restored there.
 
“Although the data in the scientific literature are contradictory, a reduction in AMPK activity is frequently observed in type 2 diabetics, and this is associated with a reduction in oxidative capacity and an increase in lipogenesis,”  says Evangelista.

The physically active group fed the Cafeteria diet showed a significant increase in AMPK , explains Evangelista, and the consequence was the maintenance of increased lipolysis, improved oxidative capacity and lower lipogenesis.

The study coordinated by Evangelista resulted in the master’s project of Talita Sayuri Higa and was conducted at the USP Physical Education and Sports School. The preliminary data were presented at the 27th Annual Meeting of the Federation of Experimental Biology Societies (FeSBE) held in Águas de Lindoia in August, at which the study received an honorable mention.

“The next step is to better understand the impact of exercise on the metabolism of skeletal muscle tissue in order to uncover how adipose tissue and skeletal muscle tissue cooperate to prevent metabolic disease,”  explains Evangelista.